Selective inhibition of adenylyl cyclase type V by the dopamine D, receptor

Despite a great deal of research, the second messenger cou-pling of the dopamine D3 receptor has not yet been clearly established. The closely related D2 and D4 receptors have been shown to inhibit adenylyl cyclase activity in a variety of cell types, but the D3 receptor has little or no effect on this second messenger system. We now demonstrate that when the D3 receptor and adenylyl cyclase type V are coexpressed in 293 cells, the agonist quinpirole causes 70 % inhibition of forskolin-stimulated cAMP levels. This effect seems to be selective for this adenylyl cyclase isoform because the D3 receptor does not inhibit adenylyl cyclase types I or VI and only weakly stimulates adenylyl cyclase type II. In contrast, the D2 receptor inhibits cAMP accumulation in 293 cells in the absence of cotrans-fected adenylyl cyclases and stimulates adenylyl cyclase type II to a greater extent than the D3 receptor. The inhibition o